The Minnesota ACTU seeks to continue participation in the ACTG. Ours is a comprehensive unit with a clinical core that has enrolled 421 patients (265 active) as of July 29, 1991, an HIV Laboratory consistently certified for antigen and culture that has participated in regional batch testing and innovated new procedures including an HIV microculture assay, a Pharmacology Laboratory doing antiviral levels testing for ACTUs regionally as well as performing complex on-site pharmacokinetics as required in Phase I protocols, and a Neurology component consisting of the originators and directors of the ACTG Neurology Consortium. During the 4-year renewal period, our ACTU will enroll 90-100 new patients/year. Minority enrollments will be increased by making Hennepin County Medical Center (HCMC), where the largest percentage of our potential minority subjects are seen, a full-fledged subunit with additional on-site staffing. HCMC's role has also been enhanced by appointing Dr. Margaret Simpson, HCMC STD Clinic director, as overall ACTU clinical director. We will also intensify our recruitment efforts at St. Paul Ramsey Medical Center (SPRMC), which has a large number of minority patients. To date, SPRMC has referred more than 100 patients for ACTG studies. Four developmental studies are planned: 1) HIV strains from ACTG patients will be tested using a highly-reproducible and quality-controlled sensitivity method to investigate the clinical significance of HIV resistance to antiretroviral drugs. Other phenotypic and genotypic changes associated with HIV resistance will be characterized; 2) Pharmacology research will optimize dosing of antiretrovirals by studying the pharmacodynamics of targeted dosing strategies rather than a "single dose for all". Pharmacology will also explore the pharmacodynamics of intracellular concentrations of antivirals and how these relate to plasma concentrations; 3) A prospective study is planned to investigate early detection, quantitation, and predictive value of CMV viremia in the development of CMV disease (the most common viral OI in HIV/AIDS). Quantitative virology for HIV and CMV will be done to delineate the role of CMV as a cofactor promoting replication of HIV; and 4) A Neurology Coordinating Center will be established to function as a "reference laboratory", training personnel at other ACTUs and providing consultation in the development and implementation of clinical trials directed at the AIDS Dementia Complex and other neurological complications of HIV infection.